Background: s/Aims: The patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M variant has been implicated in metabolic dysfunction-associated steatotic liver disease (MASLD), but its role in hepatocellular carcinoma (HCC) development is unclear. This study examines the association between the PNPLA3 I148M variant and HCC occurrence. Methods: A total of 562 MASLD patients, with and without HCC, were prospectively and consecutively enrolled at two universityaffiliated hospital between June 2024 and June 2025. Genomic DNA was extracted from buccal swabs or liver biopsy samples, and single nucleotide polymorphism genotyping was performed to determine the rs738409 genotype at codon 148 of PNPLA3. The histological grade of HCC was assessed using the Edmondson-Steiner (ES) grading system in patients who underwent core-needle liver biopsy. Results: Among 474 non-HCC patients, the GG genotype was found in 39.9%, GC in 37.1%, and CC in 23.0%. In 88 HCC patients, these frequencies were 45.5%, 36.4%, and 18.2%, respectively. No significant differences in GG genotype distribution were observed between HCC and non-HCC groups (P=0.509), nor in subgroups by sex, age, obesity status, cirrhosis status, fibrosis-4 index, or liver stiffness measurement. However, among HCC patients with histological grading, the GG genotype was significantly associated with higher ES grades (P=0.0076). Conclusions The PNPLA3 I148M GG genotype was not significantly associated with increased HCC occurrence in Korean MASLD patients within the present cohort. Although the GG genotype is known to play a role in development and progression of MASLD, further studies are warranted to clarify its contribution to tumor initiation and dedifferentiation.

Background/Aims: Although numerous noninvasive steatosis indices have been developed to assess hepatic steatosis, whether they can be applied to young adults in the evaluation of metabolic dysfunction-associated steatotic liver disease (MASLD) remains uncertain. Methods: Data from patients under 35 years of age who visited the Liver Health Clinic at the Armed Forces Goyang Hospital between July 2022 and January 2024 were retrospectively collected. Steatosis was diagnosed on the basis of a controlled attenuation parameter score ≥250dB/m. MASLD was defined as the presence of steatosis in patients with at least one cardiometabolic risk factor. Results: Among the 1,382 study participants, 901 were diagnosed with MASLD. All eight indices for diagnosing steatosis differed significantly between the MASLD and non-MASLD groups (p<0.001). Regarding the predictive performance, the hepatic steatosis index (HSI), fatty liver index (FLI), Framingham steatosis index, Dallas steatosis index, Zhejiang University index, lipid accumulation product, visceral adiposity index, and triglyceride glucose-body mass index exhibited an area under the curve of 0.898, 0.907, 0.899, 0.893, 0.915, 0.869, 0.791, and 0.898, respectively. The cutoff values for the FLI and HSI were re-examined, indicating a need for alternative cutoff values for the HSI, with a rule-in value of 42 and a rule-out value of 36 in this population. Conclusions This study presents novel findings regarding the predictive performance of established steatosis markers in young adults. Alternative cutoff values for the HSI in this population have been proposed and warrant further validation.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Background/Aims: Although numerous noninvasive steatosis indices have been developed to assess hepatic steatosis, whether they can be applied to young adults in the evaluation of metabolic dysfunction-associated steatotic liver disease (MASLD) remains uncertain. Methods: Data from patients under 35 years of age who visited the Liver Health Clinic at the Armed Forces Goyang Hospital between July 2022 and January 2024 were retrospectively collected. Steatosis was diagnosed on the basis of a controlled attenuation parameter score ≥250dB/m. MASLD was defined as the presence of steatosis in patients with at least one cardiometabolic risk factor. Results: Among the 1,382 study participants, 901 were diagnosed with MASLD. All eight indices for diagnosing steatosis differed significantly between the MASLD and non-MASLD groups (p<0.001). Regarding the predictive performance, the hepatic steatosis index (HSI), fatty liver index (FLI), Framingham steatosis index, Dallas steatosis index, Zhejiang University index, lipid accumulation product, visceral adiposity index, and triglyceride glucose-body mass index exhibited an area under the curve of 0.898, 0.907, 0.899, 0.893, 0.915, 0.869, 0.791, and 0.898, respectively. The cutoff values for the FLI and HSI were re-examined, indicating a need for alternative cutoff values for the HSI, with a rule-in value of 42 and a rule-out value of 36 in this population. Conclusions This study presents novel findings regarding the predictive performance of established steatosis markers in young adults. Alternative cutoff values for the HSI in this population have been proposed and warrant further validation.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background: Serum calcium and magnesium levels are a key factor of the coagulation cascade and may potentially contribute to the pathophysiology of intracerebral hemorrhage (ICH) expansion. The aim of this study was to attain and sustain target levels of serum calcium and magnesium for three days following admission. Methods: A single-blind, prospective, multicenter randomized study was conducted from 2019 to 2022 years, enrolling acute ICH patients aged 18–80 years, with radiological diagnosis and without surgical intervention. Participants were randomly assigned in a 1:1 ratio to either the study group or the control group. In the study group, the target serum levels of calcium (9–10.2 mg/dL) and magnesium (2–3 mg/dL) were actively achieved and maintained for a duration of 3 days following admission. The primary outcome was the expansion of ICH volume within the first 3 days between the study group and the control groups. Results: After implementing inclusion/exclusion criteria, 105 of 354 patients remained in the study. There were no significant differences in ICH volume on hospital days 2 and 3 between the groups. Admission factors including Glasgow coma scale score, hemoglobin level, ICH volume, and spot sign showed significant correlations in multivariate analysis. On the third day of hospitalization, admission serum magnesium levels showed a significant correlation with ICH expansion, whereas calcium levels did not. Conclusion Admission serum magnesium levels were found to correlate with hematoma expansion in patients with acute ICH. While magnesium itself may not be a direct therapeutic target, it could serve as a valuable indicator for identifying potential therapeutic strategies aimed at preventing ICH volume increase.

Background/Aims: Although numerous noninvasive steatosis indices have been developed to assess hepatic steatosis, whether they can be applied to young adults in the evaluation of metabolic dysfunction-associated steatotic liver disease (MASLD) remains uncertain. Methods: Data from patients under 35 years of age who visited the Liver Health Clinic at the Armed Forces Goyang Hospital between July 2022 and January 2024 were retrospectively collected. Steatosis was diagnosed on the basis of a controlled attenuation parameter score ≥250dB/m. MASLD was defined as the presence of steatosis in patients with at least one cardiometabolic risk factor. Results: Among the 1,382 study participants, 901 were diagnosed with MASLD. All eight indices for diagnosing steatosis differed significantly between the MASLD and non-MASLD groups (p<0.001). Regarding the predictive performance, the hepatic steatosis index (HSI), fatty liver index (FLI), Framingham steatosis index, Dallas steatosis index, Zhejiang University index, lipid accumulation product, visceral adiposity index, and triglyceride glucose-body mass index exhibited an area under the curve of 0.898, 0.907, 0.899, 0.893, 0.915, 0.869, 0.791, and 0.898, respectively. The cutoff values for the FLI and HSI were re-examined, indicating a need for alternative cutoff values for the HSI, with a rule-in value of 42 and a rule-out value of 36 in this population. Conclusions This study presents novel findings regarding the predictive performance of established steatosis markers in young adults. Alternative cutoff values for the HSI in this population have been proposed and warrant further validation.